Alterations in longevity of specific neurons may bring about severe behavioral deficits of a mature organism. The investigations proposed here will study the question of whether changes in position and cellular interactions will affect survival of dopaminergic neurons. Immunocytochemical and histochemical approaches are to be used to identify dopaminergic and putative cholinergic neurons. Experimental perturbation of the dopaminergic neuron systems will be carried out by neonatal lesions and transplantation techniques. Developing mesencephalic dopaminergic neurons will be partially deafferented in situ or transplanted to various regions of the brain of newborn rats. Initally these studies will test the influence of variable environmental conditions (e.g. different host brain areas, differences in the types of afferent fibers) on the connection plasticity of dopaminergic neurons and their effect on longevity of such neurons. Qualitative and quantitative analysis will be carried out at light and electron microscopic levels. Following the above procedures, the effect of cell interactins between dopaminergic neurons and putative cholinergic cells (striatal, tectal) will be investigated in co-grafts and reaggregation grafts. Since synapses are the morphological entities that signify neuron interactions, particular emphasis is placed on observations at the fine structural level.